Proteomic analysis of maternal separation-induced striatal changes in a rat model of ADHD: The spontaneously hypertensive rat

• Striatal protein expression in SHR suggests altered dopamine transporter availability.
• Striatal protein expression in SHR suggests delayed neural maturation.
• Maternal separation produces opposite effects on SHR compared to WKY and SD comparator strains.

BackgroundDevelopmental stress increases the risk of developing psychological disturbances and is modelled in rodents by maternal separation (MS). Attention-deficit/hyperactivity disorder (ADHD) is characterised by inattention, hyperactivity and impulsivity and is studied using the spontaneously hypertensive rat (SHR). Previous studies suggested that SHR differ from their progenitor strain, the Wistar-Kyoto (WKY), in their response to developmental stress. This study sought to investigate the effects of MS on striatal protein expression, a brain area implicated in the pathophysiology of ADHD and susceptible to developmental stress, in SHR, WKY and Sprague-Dawley (SD) rat strains.MethodDissected striata of separated and non-separated SHR, WKY and SD (n = 6 per group) were assessed for MS-induced changes in protein expression using isobaric tagging (iTRAQ) and peptide quantification via matrix-assisted laser desorption/ionisation (MALDI) tandem mass spectrometry.ResultsStrain and MS-induced differences were observed in proteins related to energy metabolism, neuroprotection, protein folding, protein metabolism, signalling and structure. Striatal SHR protein levels were consistent with delayed neuronal maturation and altered neurotransmission and energy metabolism. MS produced mostly opposite effects on SHR striatal proteins compared to WKY and SD.Comparison with existing methodsProteomic profiling of protein expression in selected brain areas provides an assessment of overall changes in metabolic pathways that cannot be determined using standard protein isolation techniques. Furthermore, MS-induced changes in protein expression in the striatum of SHR, WKY and SD have not been reported.ConclusionsThe results suggest that energy metabolism, neurotransmission and neural development are altered in SHR striatum and that WKY and SD are suitable comparator strains for SHR. The strain-dependent effects of MS on striatal protein expression reinforce the importance of gene × environment interactions in determining behavioural outcome.